For more than 100 years scientists have studied the sympathetic nervous system and its cardiovascular control mechanisms. Muscle sympathetic activity is the most important direct and rapidly responding variable for evaluation of sympathetic neural outflow. Therefore, anesthesiologists have been interested in the effects of anesthetics on muscle sympathetic activity at rest and during cardiovascular challenges. This review summarizes effects of positive pressure ventilation, intravenous and inhalational anesthetics as well as nitrous oxide on sympathetic muscle outflow. The least depression of both resting sympathetic outflow and its response to challenges is observed following administration of etomidate, ketamine, or a combination of low dose isoflurane/nitrous oxide and opioids. Thus, these anesthetics can be recommended for anesthesia in patients with already activated sympathetic outflow to maintain arterial blood pressure.